Comparison of Oncological and Functional Outcomes of Radical Versus Partial Nephrectomy for cT1b Renal Cell Carcinoma: A Two-Centre, Matched Analysis

INTRODUCTION

Renal cell carcinoma (RCC) represents approximately 3% of all malignancies, with nearly 138,611 new cases in Europe in 2020 [1, 2]. Up to 25% of these cases are staged cT1b, with surgical treatment options consisting of partial nephrectomy (PN) or radical nephrectomy (RN) [3, 4]. It remains unclear which patients with cT1b tumours benefit most from PN versus RN considering oncological outcomes and kidney function.

According to European Association of Urology (EAU) guidelines, PN is advised for cT1b tumours when technically feasible, in order to preserve maximum kidney function. PN is recognized to be a more complex and challenging surgery than RN, resulting in a higher postoperative complication rate [5, 6]. Thus, it is important to weigh potential risk factors and perioperative morbidities associated with PN during treatment planning. Moreover, a positive surgical margin (PSM) is discovered in 4–7% of patients after PN, which is correlated with (local) recurrence [7–9]. The occurrence of PSM after RN is rare [10]. To date, there is one randomized controlled trial (RCT) comparing RN with PN which included only tumours ≤5 cm. A lower incidence of renal dysfunction was observed after PN compared to RN [11, 12]. Survival analysis demonstrated comparable cancer-specific survival (CSS) rates for PN vs. RN. Meta-analyses show conflicting results regarding survival rates for PN vs. RN, thus it is difficult to draw definitive conclusions regarding the oncological outcomes of these procedures [13, 14]. Moreover, robust data is still missing regarding kidney function reduction after RN or PN for cT1b tumours. This study aims to compare oncological, operative and functional outcomes for cT1b tumours treated by RN or PN.

METHODS

This study was approved by the review board of both institutions. Data was retrieved from a retrospective database consisting of patients who underwent PN or RN due to clinical suspicion for RCC between 2010 and 2022. Patients with clinical suspicion for RCC staged cT1bN0/xM0/x, who were ≥18 years of age at the time of surgery and underwent elective PN or RN were included. All data was collected retrospectively by reviewing electronic patient medical records and importing data into Castor EDC. Exclusion criteria are listed in Fig. 1. Patient characteristics included age, gender, American Society of Anaesthesiologists (ASA) score, Charlson Comorbidity Index age-adjusted (CCI-A), body mass index (BMI), pre-operative serum creatinine (sCr) and eGFR according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [15]. All patients received preoperative contrast-enhanced CT or MRI for tumour size, TNM classification and nephrometry scores (RENAL score, PADUA score) [16, 17]. Selection for PN or RN was done based on EAU guidelines and patient characteristics. Follow-up check-ups were done depending on the risk group, as reported in the EAU guidelines. The following risk groups were used: low, intermediate and high risk. For patients with clear-cell RCC this was done according to the Leibovich score. For remaining patients the following classification was used: low risk: pT1a-b/pNx-0 M0 and histological grade 1 or 2; intermediate risk: pT1b pNx-0 and/or histological grade 3-4; high risk: pT1-pT4 with any histological grade or pT any, pN1 cM0 with any histological grade [18]. Follow-up data including sCr, eGFR, (local) recurrence status and radiological results were retrieved from these check-ups. Local recurrence was defined as RCC recurrence in the operated kidney or renal fossa. In case of doubt regarding PSM based on the pathology report, the slides were re-examined by the pathologist.

Fig. 1

Selection of the study population.

3RESULTS

A total of 386 patients with a cT1b tumour underwent RN or PN during the study period, of whom 145 were excluded because they did not meet the inclusion criteria. Propensity scores were generated for the remaining 241 patients with cT1b tumours. After matching there were 100 patients in each treatment group (Fig. 1).

3.3Survival outcomes

The median follow-up was similar in both groups (RN 38 [17–66]; PN 42 months [14–74>]). During the 10-year follow-up period seven patients died in the RN group versus 9 patients in the PN group. Of the deaths within the RN group, three were RCC-related, three were of other causes and one death was unknown. Among the patients who underwent PN, two deaths were RCC related, four were non-RCC related and in three cases the cause of death was unknown. There were no significant differences observed in survival rates between the two cohorts regarding RFS, OS and CSS (Fig. 2A–C). Cox univariate and multivariate regression analyses showed high risk group (Hazard rate [HR] = 7.8, p = 0.005) as a predictor of OS. Postoperative eGFR or CKD group was not predictive of OS. Intermediate (HR 3.2, p = 0.018) and high risk groups (HR 5.5, p = 0.013) were both predictors of RFS (Supplementary tables 1a–c). Local recurrence occurred only in the PN group (8% vs. 0%), as shown in Table 3.

Fig. 2

A–C: Kaplan-Meier estimates of recurrence-free survival (adjusted for risk group) (A), overall survival (B), cancer-specific survival (C).

Table 3

Recurrences (%) after RN and PN

Risk group n (% within risk group)	RN	PN	p-value
Low	0 (0)	7 (12)	0.01
Intermediate	5 (15)	5 (19)	0.68
High	2 (29)	1 (20)	0.83
Total n (%)	7 (8)	13 (14)	0.10
Progression type n (L(ow), M(edium), H(igh) risk group)			0.01
Local recurrence	0	8 (6 L, 1 M, 1 H)
Contralateral kidney	1 (0 L, 1 M, 0 H)	2 (0 L, 2 M, 0 H)
Metastasis	6 (0 L, 4 M, 2 H)	3 (1 L, 2 M, 0 H)

Risk groups according to EAU guidelines. Risk groups for clear-cell RCC are based on the Leibovich score. For other RCC subtypes the risk groups are based on pathological TNM stage and nuclear grade.

3.4Kidney function outcomes

The RN group showed a significant reduction in eGFR, from a median of 83 at baseline to an eGFR of 57 at 1-year post-surgery (p < 0.001). The relative reduction of eGFR after one year was higher for RN (31%) compared to PN (13%, p < 0.001). Significantly more patients developed new-onset CKD ≥3b (defined as eGFR < 45) after RN (n = 18 [22% ]) compared to PN (n = 3 [4% ]) (p < 0.001). Of patients with a preoperative CKD stage 2, 29% developed a CKD≥3b after RN, compared to 5% after PN. Kidney function outcomes are summarized in Table 4. A relative decline of 31% in eGFR compared to baseline was seen after RN, compared to 13% after PN 1-year post-surgery and remained stable during the 5-year follow-up. At 5 years follow-up the difference in mean eGFR between the PN and RN group was 15 (Fig. 3).

Table 4

Renal function outcomes after RN vs. PN for cT1b tumours, including migration of CKD stage post-surgery

	RN		PN
Pre-op	1-year post-op	p-value	Pre-op	1-year post-op	p-value
New-onset CKD≥3b n (%)	18 (22)			3 (4)		<0.001
Pre-op CKD1 (eGFR≥90)	0 (0)			0 (0)
Pre-op CKD2 (eGFR 60–89)	12 (29)			2 (5)
Pre-op CKD3a (eGFR 45–59)	6 (100)			1 (11)
eGFR median (IQR)	83 (69–95)	57 (44–65)	<0.001	84 (72–95)	73 (60–87)	<0.001
sCr median (IQR)	81 (69–92)	107 (92–127)	<0.001	79 (71–94)	88 (73–104)	<0.001
Change eGFR (%)	31			13		<0.001
Median change eGFR (IQR)	28 (18–34)			8 (2–16)		<0.001
Change sCr (%)	27			10		<0.001
Median change sCr (IQR)	32 (22–41)			8 (1–16)		<0.001

eGFR in ml/min/1.73 m², sCr: serum creatinine (mg/dl), CKD: chronic kidney disease.

Fig. 3

Renal function during 5-year follow-up period after RN vs. PN. Mean eGFR during 5-year follow-up, error bars represent 95% confidence interval (CI).

DISCUSSION

Our matched analysis showed that PN has superior renal function compared to RN in a 5-year follow-up of patients with suspected T1b RCC. The eGFR stabilized at 6–12 months after surgery in both groups, though, eGFR remained significantly reduced after RN compared with PN. These results are similar to the findings described by others [11, 21]. The EORTC 30904 trial showed that PN reduced the incidence of at least moderate renal dysfunction (eGFR < 60), though this was not the case for advanced kidney disease (eGFR < 30) or kidney failure (eGFR < 15) [11]. Some retrospective studies suggest preserved kidney function can lower the risk of cardiovascular events, improving the quality of life (QoL) and improving survival compared to RN [22–24]. Despite the significant decline in renal function and higher rates of new-onset CKD in the RN group, we did not observe a worse OS. This aligns with Lane et al., who concluded that surgical-induced CKD may have better survival outcomes than medically-induced CKD [25]. However, they did observe an impaired survival in case of postoperative eGFR <45. This highlights the importance of accurate prediction of postoperative eGFR. Our study revealed that 22% of patients who underwent RN had a postoperative eGFR of <45, all of whom had a preoperative eGFR <90. Moreover, this suggests that RN is a viable option for patients with good preoperative kidney function. Nevertheless, information on QoL, previous medical history or cardiovascular events was not measured in this study and must be considered when choosing between PN and RN [26]. The current PARTIAL randomized controlled trial analyses renal function and QoL after PN versus RN in patients with tumours ≤7 cm and might lead to new insights [27].

Previous studies comparing RN and PN for T1b tumours showed contradictory results regarding survival. The EORTC trial showed a worse OS for PN compared to RN, however this effect was no longer significant in the targeted RCC population [12, 28]. Two meta-analyses comparing PN and RN for T1b tumours showed similar CSS, RFS and OS rates [13, 14]. We also found comparable results: OS, CSS and RFS rates did not differ between PN and RN, suggesting that PN is a justified treatment option when considering oncological outcomes while maintaining kidney function. Even though we did not find a significant difference in RFS between RN and PN, local recurrences were significantly more frequent in the low-risk group after PN compared to RN. There were no differences in recurrence rates in the intermediate and high-risk groups. Seven recurrences in the low-risk group were seen, of which six were local recurrence. The remaining patient developed retrocaval lymph node metastases. The reason for this higher (local) recurrence rate remains unclear. Only one of the six patients with PSM had a local recurrence during follow-up, thus this does not justify the higher recurrence rate in the PN group. This patient had an intraperitoneal tumour deposition one year post-surgery for which he underwent a metastasectomy. Currently the patient is under surveillance without active treatment. In the current study the exact value of PSM remains unclear and therefore not justifies a secondary RN, as it was not predictive of CSS or RFS. No predictive factors were found for PSM. Another secondary outcome of this study was the postoperative complication rate. PN is a more complex intervention than RN with a higher complication rate [6]. There were significantly more complications in the PN group compared to the RN group. This is in accordance with other studies that looked at surgical outcomes for T1b tumours [29, 30]. There were two complications classified as CD grade 4. In one case the patient had to be re-intubated immediately after surgery due to swelling of the adenoids, in the other case the patient developed an ileus for which a laparotomy was indicated, in addition to urine leakage and an abscess that had to be drained. It is crucial to critically assess the elevated risk of complications following PN, since the increased risk may not always outweigh the benefits of kidney function preservation. The estimated blood loss was also significantly higher in the PN group, though its clinical significance is debatable.

This study is not devoid of limitations. The most important limitation is the retrospective design. We attempted to minimize treatment selection bias by using propensity score matching to adjust for confounding variables. For example, both nephrometry scores were significantly higher in the RN group, despite propensity score matching. These higher scores confirm RN as the preferred method for more complex tumours in daily practice. Nonetheless, recent data shows that increasing RENAL score does not compromise oncological outcomes [31]. Furthermore, unmeasured confounding variables may still be present. Moreover, despite all surgeries being conducted by experienced urologists, a learning curve for the PN procedure as well as the transition from open and laparoscopic to the robotic approach may have influenced the results. Lastly, survival analyses should be interpreted with caution, as the event numbers of CSS are small.

CONCLUSION

Survival rates are similar for patients with cT1b tumours undergoing PN or RN. Despite more local recurrences in the PN group, the comparable survival estimates suggest that local salvage options are effective. PN has superior preservation of renal function compared to RN, though it could be argued that RN is preferable when maintenance of renal function is not a priority.